(Hypertension. 1999;33:440-445.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Local Renal Medullary L-NAME Infusion Enhances the Effect of Long-Term Angiotensin II Treatment
From the Clinical Research Deptartment, 2nd Institute of Physiology, Semmelweis University of Medicine, Budapest, Hungary (M.S.); Laboratorio de Cardiovascular, Department de Fisiologia, ICBS, UFRGS, Brasil (C.Y.M.); and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wis (A.W.C.).
Correspondence to Mátyás Szentiványi, Jr, MD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, PO Box 26509, Milwaukee, WI 53226-0509. E-mail szentiva{at}mcw.edu
Abstract—We hypothesized that
the relatively high doses of angiotensin (Ang) II required
to produce hypertension in rats were related to stimulation of renal
medullary nitric oxide production, which in turn blunted
reductions in medullary blood flow and the development of hypertension.
Ang II was infused (5 days at 3 ng · kg-1 ·
min-1 IV) to uninephrectomized Sprague-Dawley rats in the
presence and absence of a continuous medullary interstitial
NG-nitro-L-arginine methyl ester
(L-NAME) infusion. Renal cortical and medullary blood flows were
determined with the use of implanted optical fibers and
laser-Doppler flowmetry. Ang II in the absence of medullary
nitric oxide synthase inhibition did not change cortical or medullary
blood flow or mean arterial pressure. A threshold dose of
L-NAME was determined (75 µg · kg-1 ·
h-1) that did not produce significant short- or long-term
changes in medullary blood flow and mean arterial pressure.
In rats with blunted medullary nitric oxide synthase activity, Ang II
infused intravenously resulted in a 30% reduction in
medullary blood flow (from 1.3 to 0.9±0.2V) and 
20 mm Hg
increase in mean arterial pressure with Ang II infusion
over 5 days. During 70 minutes after the start of
intravenous Ang II, there was an immediate reduction in
medullary blood flow, with no changes in cortical blood flow or mean
arterial pressure. We conclude that the relative
insensitivity of rats to long-term elevations of circulating Ang II is
due to the potent counterregulatory actions of the nitric oxide system,
specifically within the renal medulla. The results provide novel
insights of how the organism attempts to protect itself from the
hypertensive effects of Ang II.
Key Words: hypertension, renal • kidney • angiotensin II • renal blood flow • nitric oxide • nitric oxide synthase
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